In order to make informed public health decisions based on cost-effectiveness analyses, new simulation models of HPV and cervical cancer need to be created by decision analysts who have expertise across a broad array of subjects that reflects the complexity of HPV and cervical cancer, including virology, molecular cancer biology and computational biology. The purpose of this NCI Career Development Award (CDA) is to develop substantive and methodological expertise that will aide in constructing and analyzing mathematical models of cancer, with a particular focus on cervical cancer. The training aspect of this CDA will provide the recipient with training in three key areas (that can also be applied to other cancers besides cervical cancer): 1) use of mathematics to model biologic processes (computational biology); 2) molecular cancer biology; and 3) virology, including viral ecology and evolutionary virology. The knowledge and skills gained during this CDA will enable the recipient to build more sophisticated cost-effectiveness models of HPV and cervical cancer. The models will be updated to reflect new insights into the natural history of HPV. In contrast to other cost-effectiveness models, this model will include non-HPV co-factors for progression to pre-cancer and cancer such as smoking, type-specific HPV infection, as well as an HPV competition model to examine the potential long-term impact of a vaccine. This model will be used to inform epidemiologic studies about the natural history of HPV. It will also be used to examine potential gains from targeted screening of women at high-risk of pre-cancer and cancer and to determine the most effective and cost-effective primary and secondary prevention strategies, based on recent and ongoing advances in the field. Additionally, insights gained from constructing and analyzing the model will be used as the basis for a R01 proposal. The proposed research is of public health relevance because cervical cancer prevention strategies are rapidly adapting to the discovery of the necessary causal role of oncogenic human papillomavirus (HPV) infections. A 50-year reliance on cytology, followed by colposcopically-directed biopsy and destructive treatment, is yielding to primary prevention by vaccination and secondary prevention by screening based at least partly on HPV testing. For a rational shift in public health practice, we will need an evaluation of the new primary and secondary prevention methods; part of this evaluation will involve cost-effectiveness analyses using sophisticated simulation models.